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Original article
Short- and long-term effects of erythropoietin treatment on endothelial progenitor cell levels in patients with cardiorenal syndrome
  1. Kim E Jie1,
  2. Karien van der Putten2,3,
  3. Marloes W T Bergevoet1,
  4. Pieter A Doevendans4,
  5. Carlo A J M Gaillard3,5,
  6. Branko Braam6,
  7. Marianne C Verhaar1
  1. 1Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands
  2. 2Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands
  3. 3Department of Internal Medicine, Meander Medical Center Amersfoort, Amersfoort, the Netherlands
  4. 4Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
  5. 5Department of Nephrology, VU University Medical Center Amsterdam, the Netherlands
  6. 6Department of Medicine, Division of Nephrology and Immunology, University of Alberta, Edmonton, Canada
  1. Correspondence to Marianne C Verhaar, Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands; m.c.verhaar{at}


Objective Patients with cardiorenal syndrome (CRS) have high cardiovascular morbidity. Endothelial progenitor cells (EPC) constitute an endogenous vascular repairsystem, protecting against atherosclerosis development. Erythropoietin (EPO) treatment may have beneficial effects by mobilizing EPC from the bonemarrow. Our objective is to determine EPC levels and effects of EPO therapy on EPC levels in CRS patients.

Design Open-label randomized trial.

Setting Part of the EPOCARES-trial, conducted in Utrecht (Netherlands).

Patients Patients with CRS and anaemia and healthy controls were included.

Interventions Patients were randomized to receive EPO therapy (50 IU/kg/wk) for 52 weeks or no EPO therapy.

Main outcome measures CD34+KDR+-EPC, cultured EPC outgrowth and function at baseline, after 18 days and after 52 weeks.

Results Patients showed lower CD34+KDR+-cell numbers compared to controls (6(12) vs. 19(19) cells/105 granulocytes; p=0.010), despite increased levels of stromal cell-derived factor-1α; (3.1(0.8) vs 2.6(0.3) ng/ml; p=0.001). EPC outgrowth and function were not different between patients and controls. EPC levels did not change after 18 days with or without EPO treatment. CD34+KDR+-cells significantly declined after 52 weeks in the non-treated group (p=0.028). Long-term EPO therapy did not significantly affect this reduction in CD34+KDR+-EPC levels.

Conclusions CRS patients showed reduced CD34+KDR+-EPC levels compared to controls, consistent with a reduced vascular regenerative potential and despite upregulated SDF-1α levels. Over a one-year follow-up period a marked 68% further reduction in EPC levels was observed in the patient group without EPO treatment. In spite of promising experimental studies, our longitudinal, randomized study did not show significant influence of either short- or long-term EPO therapy on reduced EPC levels in CRS patients.

  • Renal disease
  • atherosclerosis
  • endothelium

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    • Funding This work was supported by the Netherlands Heart Foundation (grant number 2005B192); an unrestricted grant from Roche; the Netherlands Organisation for Scientific Research (Vidi grant number 016.096.359 to MCV); and the University Medical Center Utrecht (MD/PhD fellowship to KEJ).

    • Competing interests None declared.

    • Ethics approval The protocol was approved by the medical ethics committee and all patients gave informed consent. Procedures were in accordance with the Helsinki Declaration.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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